Efficacy, toxicity and prognostic factors of pyrotinib‑involved neoadjuvant therapy in HER2‑positive breast cancer: A retrospective study

Wang,Hao; Cao,Hailing; Guo,Zhiyun

doi:10.3892/ol.2023.13900

Efficacy, toxicity and prognostic factors of pyrotinib‑involved neoadjuvant therapy in HER2‑positive breast cancer: A retrospective study

Authors:
- Hao Wang
- Hailing Cao
- Zhiyun Guo
View Affiliations

Affiliations: Department of Pathology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong 511400, P.R. China, Department of Thyroid and Breast Surgery, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong 511400, P.R. China, Department of Pathology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong 511400, P.R. China
Published online on: June 6, 2023 https://doi.org/10.3892/ol.2023.13900
Article Number: 314
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Pyrotinib is a novel irreversible tyrosine kinase inhibitor targeting the human epidermal growth factor receptor (HER), whose efficacy in treating metastatic HER2‑positive (HER2⁺) breast cancer has been confirmed. The present study aimed to explore the efficacy, safety and prognostic factors of pyrogenic‑involved neoadjuvant therapy in patients with HER2+ breast cancer. A total of 49 patients with HER2+ breast cancer who received pyrotinib‑neoadjuvant therapy were recruited. All patients received pyrotinib plus chemotherapy with or without trastuzumab neoadjuvant treatment for six cycles (21 days/cycle). Concerning the clinical response, 4 (8.2%), 36 (73.4%) and 9 (18.4%) patients achieved complete response, partial response and stable disease after 6‑cycle pyrotinib‑neoadjuvant treatment, respectively; the objective response rate and disease control rate reached 81.6 and 100.0%, respectively. Concerning the pathological response, 23 (46.9%), 12 (24.5%), 12 (24.5%) and 2 (4.1%) patients were evaluated as Miller‑Payne grade 5, 4, 3 and 2, respectively. In addition, 23 (46.9%) patients achieved pathological complete response (pCR) in the breast tissue, 40 (81.6%) patients achieved pCR in lymph nodes, while 22 (44.9%) patients obtained total pCR (tpCR). Further multivariate logistic regression analysis demonstrated that pyrotinib plus trastuzumab and chemotherapy (vs. pyrotinib plus chemotherapy) was independently correlated with increased tpCR (P=0.048). The most frequent adverse events included diarrhea (81.6%), anemia (69.4%), nausea and vomiting (63.3%), and fatigue (51.0%). The majority of the adverse events were mild and controllable. In conclusion, pyrotinib‑neoadjuvant therapy presented optimal efficacy and mild toxicity in patients with HER2⁺ breast cancer, whose efficacy was affected by the combination treatment with trastuzumab.

View Figures

View References

1	Watkins EJ: Overview of breast cancer. JAAPA. 32:13–17. 2019. View Article : Google Scholar : PubMed/NCBI
2	Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N and Chen W: Cancer statistics in China and United States, 2022: Profiles, trends, and determinants. Chin Med J (Engl). 135:584–590. 2022. View Article : Google Scholar : PubMed/NCBI
3	Peddi PF and Slamon DJ: Frontiers in HER2-positive breast cancer in 2020. Curr Opin Obstet Gynecol. 33:48–52. 2021. View Article : Google Scholar : PubMed/NCBI
4	Goutsouliak K, Veeraraghavan J, Sethunath V, De Angelis C, Osborne CK, Rimawi MF and Schiff R: Towards personalized treatment for early stage HER2-positive breast cancer. Nat Rev Clin Oncol. 17:233–250. 2020. View Article : Google Scholar : PubMed/NCBI
5	Takada M and Toi M: Neoadjuvant treatment for HER2-positive breast cancer. Chin Clin Oncol. 9:322020. View Article : Google Scholar : PubMed/NCBI
6	Cesca MG, Vian L, Cristóvão-Ferreira S, Pondé N and de Azambuja E: HER2-positive advanced breast cancer treatment in 2020. Cancer Treat Rev. 88:1020332020. View Article : Google Scholar : PubMed/NCBI
7	Korde LA, Somerfield MR, Carey LA, Crews JR, Denduluri N, Hwang ES, Khan SA, Loibl S, Morris EA, Perez A, et al: Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol. 39:1485–1505. 2021. View Article : Google Scholar : PubMed/NCBI
8	Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, et al: Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 19:115–126. 2018. View Article : Google Scholar : PubMed/NCBI
9	Wang H, Li Y, Qi Y, Zhao E, Kong X, Yang C, Yang Q, Zhang C, Liu Y and Song Z: Pegylated liposomal doxorubicin, docetaxel, and trastuzumab as neoadjuvant treatment for HER2-positive breast cancer patients: A phase II and biomarker study. Front Oncol. 12:9094262022. View Article : Google Scholar : PubMed/NCBI
10	Dang C, Ewer MS, Delaloge S, Ferrero JM, Colomer R, de la Cruz-Merino L, Werner TL, Dadswell K, Verrill M, Eiger D, et al: BERENICE final analysis: Cardiac safety study of neoadjuvant pertuzumab, trastuzumab, and chemotherapy followed by adjuvant pertuzumab and trastuzumab in HER2-positive early breast cancer. Cancers (Basel). 14:25962022. View Article : Google Scholar : PubMed/NCBI
11	Blair HA: Pyrotinib: First global approval. Drugs. 78:1751–1755. 2018. View Article : Google Scholar : PubMed/NCBI
12	Xuhong JC, Qi XW, Zhang Y and Jiang J: Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer. Am J Cancer Res. 9:2103–2119. 2019.PubMed/NCBI
13	Li C, Bian X, Liu Z, Wang X, Song X, Zhao W, Liu Y and Yu Z: Effectiveness and safety of pyrotinib-based therapy in patients with HER2-positive metastatic breast cancer: A real-world retrospective study. Cancer Med. 10:8352–8364. 2021. View Article : Google Scholar : PubMed/NCBI
14	Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, et al: Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): A multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 22:351–360. 2021. View Article : Google Scholar : PubMed/NCBI
15	Yao DS, Wang W, Chang JY, Zhang Y, Zhang HW, Xu JX and Cai HF: Neoadjuvant pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide for HER2-positive locally advanced breast cancer: A retrospective case-series study. Gland Surg. 10:3362–3368. 2021. View Article : Google Scholar : PubMed/NCBI
16	Xuhong J, Qi X, Tang P, Fan L, Chen L, Zhang F, Tan X, Yan W, Zhong L, He C, et al: Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for stage I–III HER2-positive breast cancer: A phase II clinical trial. oncologist. 25:e1909–e1920. 2020. View Article : Google Scholar : PubMed/NCBI
17	Tian C, Wang M, Liu H, Liu J, Xu M and Ma L: Efficacy and safety of neoadjuvant pyrotinib plus docetaxel/liposomal doxorubicin/cyclophosphamide for HER2-positive breast cancer. Ir J Med Sci. Jul 13–2022.(Epub ahead of print).
18	Liu Z, Wang C, Chen X, Zhu J, Sun X, Xia Q, Lu Z, Qiao J, Zhou Y, Wang H, et al: Pathological response and predictive role of tumour-infiltrating lymphocytes in HER2-positive early breast cancer treated with neoadjuvant pyrotinib plus trastuzumab and chemotherapy (Panphila): A multicentre phase 2 trial. Eur J Cancer. 165:157–168. 2022. View Article : Google Scholar : PubMed/NCBI
19	Cserni G, Chmielik E, Cserni B and Tot T: The new TNM-based staging of breast cancer. Virchows Arch. 472:697–703. 2018. View Article : Google Scholar : PubMed/NCBI
20	Litière S, Collette S, de Vries EG, Seymour L and Bogaerts J: RECIST-learning from the past to build the future. Nat Rev Clin Oncol. 14:187–192. 2017. View Article : Google Scholar : PubMed/NCBI
21	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
22	Zhong X, He P, Chen J, Yan X, Wei B, Zhang Z, Bu H, Li J, Tian T, Lv Q, et al: Neoadjuvant pyrotinib plus trastuzumab and nab-paclitaxel for HER2-positive early or locally advanced breast cancer: An exploratory phase II trial. Gland Surg. 11:216–225. 2022. View Article : Google Scholar : PubMed/NCBI
23	Zhang L, Wu X, Zhou J, Zhu M, Yu H, Zhang Y, Zhao Y, Han Z, Guo Y, Guan X, et al: Pyrotinib in the treatment of women with HER2-positive advanced breast cancer: A multicenter, prospective, real-world study. Front Oncol. 11:6993232021. View Article : Google Scholar : PubMed/NCBI
24	Wang C, Deng S, Chen J, Xu X, Hu X, Kong D, Liang G, Yuan X, Li Y and Wang X: The synergistic effects of pyrotinib combined with adriamycin on HER2-positive breast cancer. Front Oncol. 11:6164432021. View Article : Google Scholar : PubMed/NCBI
25	Chang J, Xu M, Wang C, Huang D, Zhang Z, Chen Z, Zhu X and Li W: Dual HER2 targeted therapy with pyrotinib and trastuzumab in refractory HER2 positive metastatic colorectal cancer: A result from HER2-FUSCC-G study. Clin Colorectal Cancer. 21:347–353. 2022. View Article : Google Scholar : PubMed/NCBI
26	Pop L, Suciu ID, Ionescu O, Ionescu P and Toader OD: The dual blockade in the neoadjuvant setting of HER-2 positive early-stage breast cancer. J Med Life. 12:329–331. 2019. View Article : Google Scholar : PubMed/NCBI
27	Ahn S, Woo JW, Lee K and Park SY: HER2 status in breast cancer: Changes in guidelines and complicating factors for interpretation. J Pathol Transl Med. 54:34–44. 2020. View Article : Google Scholar : PubMed/NCBI
28	Mao X, Lv P, Gong Y, Wu X, Tang P, Wang S, Zhang D, You W, Wang O, Zhou J, et al: Pyrotinib-containing neoadjuvant therapy in patients with HER2-positive breast cancer: A multicenter retrospective analysis. Front Oncol. 12:8555122022. View Article : Google Scholar : PubMed/NCBI
29	Li Q, Wang Y, Zhu M, Gu Y and Tang Y: Clinical observation of neoadjuvant chemotherapy with pyrotinib plus trastuzumab in HER2-positive breast cancer: A cohort study. Gland Surg. 10:3389–3402. 2021. View Article : Google Scholar : PubMed/NCBI
30	Bowen JM: Mechanisms of TKI-induced diarrhea in cancer patients. Curr Opin Support Palliat Care. 7:162–167. 2013. View Article : Google Scholar : PubMed/NCBI
31	Duan T, Cil O, Thiagarajah JR and Verkman AS: Intestinal epithelial potassium channels and CFTR chloride channels activated in ErbB tyrosine kinase inhibitor diarrhea. JCI Insight. 4:e1264442019. View Article : Google Scholar : PubMed/NCBI